R. M. Hutchinson

G-CSF after peripheral blood stem cell transplantation in lymphoma patients significantly accelerated neutrophil recovery and shortened time in hospital: results of a randomized BNLI trial.

We have undertaken a prospective randomized study in 90 patients with relapsed or resistant lymphomas to assess the value of G‐CSF (lenograstim) in the acceleration of myeloid recovery after peripheral blood stem cell transplantation (PBSCT). A common regimen of cyclophosphamide 1.5 g/m2 on day 1 and lenograstim 263 μg s.c. on days 2–10 with two aphereses on days 10 and 11 was used for stem cell mobilization. 77% of patients achieved an adequate PBSC collection in two harvests (>2 × 108 MNC/kg or >2 × 106 CD34+ cells/kg). 65 patients went on to receive high‐dose BEAM chemotherapy and engraftment data was available for 62. 34 patients had been randomized to receive lenograstim 263 μg/d s.c. and 28 to no growth factor. The median time to ANC > 0.5 × 109/l was 9 d in the lenograstim arm versus 12.5 d in the no‐lenograstim arm (P = 0.0001). This was associated with a median duration of time in hospital post PBSCT of 13 d in the lenograstim arm versus 15.5 d in the no‐lenograstim arm (P = 0.0002). Median days to platelet independence, platelet transfusions, incidence of infection and red cell transfusion were the same in both arms. These data indicate that lenograstim significantly accelerated myeloid recovery after PBSCT and shortened the duration of hospital stay.

Mitoxantrone for refractory and relapsed acute leukemia.

Seventy‐seven patients with relapsed or refractory acute leukemia and three with acute blastic chronic myeloid leukemia (CML) were treated in an open Phase II study using mitoxantrone 12 mg/m2 intravenously daily × 5 days. Complete remission (CR) was achieved in 32 of 80 (40%), including 23/45 (52%) with relapsed acute nonlymmphocytic leukemia (ANLL), four of 12 (33%) with relapsed acute lymphocytic leukemia ALL, four of 17 (24%) with ANLL refractory to daunorubicin + cytosine arabinoside, and one of three (33%) with refractory ALL. None of the patients with acute blastic CML achieved CR. Median survival time for all patients was 121 days. Median duration of complete response was 303 days with ten of 32 patients in continuing CR for periods varying from 44+ to 1210+ days. Apart from moderately prolonged hematologic suppression toxicity was mild and subjective side effects were tolerable. Mitoxantrone is an active agent in the treatment of acute leukemia and demonstrates incomplete cross resistance with duanorubicin. Mitoxantrone should be considered for first‐line therapy in ANLL.

Identification and Treatment of Anaemia in Older Patients

SummaryAnaemia in elderly patients should never be regarded as a normal physiological response to aging. Underlying causes must be investigated and treated in a similar manner to that used in younger adults. In addition to a thorough history and physical examination, basic investigations such as red cell indices and morphology, reticulocyte count, haematinic assays and occasionally bone marrow examination, will detect the underlying pathology in most cases.Anaemia may be classified, according to red blood cell mean corpuscular volume, into microcytic, macrocytic and normocytic types. Anaemia with an absolute reticulocytosis is due either to acute blood loss or haemolysis. Other anaemias, more frequently encountered in elderly patients, are hypoproliferative, and reflect depressed marrow production or impaired erythroid maturation. Examples include anaemia of chronic disease and iron deficiency and, less commonly, megaloblastic anaemia and anaemia due to primary bone marrow failure.The treatment of anaemia should aim to correct the underlying cause of the disorder and/or to improve the quality of the blood, e.g. by haematinic replacement therapy. Recombinant human erythropoietin has revolutionised the treatment of anaemia associated with chronic renal failure, while its role in other anaemias is currently under investigation. Regular blood transfusion may be required for some elderly patients with chronic anaemia. However, the attendant risks of this procedure, such as iron overload and viral hepatitis transmission, must be considered.

Mastocytosis and Co-existent Non-Hodgkin's Lymphoma and Myeloproliferative Disorders

Generalised mastocytosis is a rare condition characterised by the clinical features of the release of vasoactive peptides from tissue mast cells infiltrating in the reticuloendothelial tissues. The mast cell however appears to have its origin in the pluripotential bone marrow stem cell committed to a basophil and it is therefore not surprising that myeloproliferative and myelodysplastic disorders commonly co-exist or terminate the clinical phase of mastocytosis. Both abnormal proliferation and maturation of the myeloid committed cells are found. Non-Hodgkins lymphoma can occur before and after mastocytosis becomes manifest. While this is statistically a random event the relationship between lymphokines and mast cell differentiation and proliferation raises the possibility of a benign reactive lymphoid event eventually becoming malignant.

A new method to study the efficiency of third generation blood filters.

Summary. In order to study the efficiency of third generation blood filters we have devised a new method using 3 μm pore size polycarbonate filter membranes and a filtration chamber to trap leucocytes passing through the blood filter. The method has enabled us to make two important observations: (1) The filters function very efficiently at the start but the efficiency diminishes progressively with time. (2) When the blood flow through the filter is retarded, due to defective priming and/or filter malfunction, the filters fail even at the outset of the transfusion.

Blood findings in generalized mastocytosis: coexistent non-Hodgkin's lymphoma.

Horny & Ruck (1990) in this Journal report underlying myeloproliferative and myelodysplastic disorders in 92% of their patients with malignant mastocytosis and only 6% of those with systemic mastocytosis (SM). No case of malignant lymphoma was noted. We report here a patient with systemic mastocytosis characterized by urticaria pigmentosa-like skin lesions in which a malignant lymphoma arose and in which features of myeloproliferative disease subsequently appeared. There have been five reported cases of a non-Hodgkin’s malignant lymphoma arising in a patient with SM (Travis & Chin-Yang. 1988a.b. 1989: Marantz & Roth, 1972: Nixon, 1966). These include four cases of malignant lymphoma, lymphocytic and a single case of malignant immunoblastic lymphoma. Our patient had centroblastic-centrocytic follicular lymphoma: to date there have been no reported cases of systemic mastocytosis accompanying this histological form. In October 1986 our patient, a 63-year-old male, presented with ascites, 7 cm splenomegaly and 10 cm hepatomegaly. He had had urticaria pigmentosa for the past 30 years. A liver biopsy showed an increase in mast cells in the liver parenchyma while a lymph node biopsy, carried out at the same time, showed the features of dermatopathic lymphadenopathy, but also revealed diffuse infiltration by increased numbers of mast cells. A laparotomy was performed and revealed a diffuse tumour involving the stomach, small bowel, colon and omentum. Histology revealed a nonHodgkin’s malignant lymphoma (centroblastic-centrocytic follicular) and this diagnosis was confirmed by immunostaining on cryostat sections which showed a monoclonal proliferation of B cells, with IgM heavy chain and kappa light chain surface immunoglobulins. A diagnosis of gastric lymphoma was made and between November 1986 and July 1987 he received combination chemotherapy with CHOP and subsequently MACOP-9. There was good resolution of symptoms and the repeat abdominal CT scan showed resolution of mesenteric lymphadenopathy and hepatomegaly, though the spleen remained 4 cm enlarged. In 1988 a diagnostic and therapeutic splenectomy was carried out. The spleen histology showed infiltration with mast cells but no evidence of lymphoma. Within 10 d post splenectomy his platelet count rose to 1000 x 10y/l and remained elevated over the next 6-9 months. The white blood cell count varied from 11 to 15 x 1 Oy/l with 50% neutrophils. an occasional myelocyte and a 14% eosinophilia. The NAP score was normal. The initial bone marrow biopsies taken at the diagnosis of follicular lymphoma showed the characteristic focal aggregates of spindle shaped mast cells seen in SM. A repeat biopsy 9 months post splenectomy showed a hypercellular marrow with increase in megakaryocytes and reticulin fibres diagnostic of myeloproliferative disease-essential thrombocythaemia (ET). Foci of spindle shaped cells remained. There was no karyotypic abnormality. His thrombocythaemia was treated with a combination of cyclophosphamide and steroid and responded with a platelet count of 405 6 weeks post chemotherapy. Six months later it had risen to 850 x 10y/l. There have been several reports of haematological and solid malignancies arising in patients with SM. It is uncertain if this is an increased risk or a coincidental finding. Recent observations suggest that SM is a myeloproliferative disease and that mast cells have a common stem cell origin with myeloid erythroid and megakaryocytic cell lines (Travis & Chin-Yang, 1988a). Horny & Ruck (1 990) describe acute and chronic myeloproliferative disease (MPD) in 12/16 of their cases of malignant mastocytosis. There were 10 chronic myeloid leukaemia. one polycythaemia rubra Vera and one myelofibrosis. It has also been suggested that ‘mast cells may produce factors that induce the proliferation of other cell lines possibly even having a gene altering effect’ (Travis & ChinYang. 1988b). However, SM may represent a more fundamental abnormality in the pluripotent stem cell, leading to association with lymphomas as well as myeloid neoplasms. In our patient the platelet count continues to rise. There is no clonal marker and so it is unclear whether he has primary ET or part of the spectrum of SM. Depart men ts of Histopat hology . *Clinical Haematology and Leicester Royal Infirmary. Leicester LEI 5 WW P. H. M. KING R. M. HUTCHINSON*

INTENSIVE INDUCTION CHEMOTHERAPY IN ELDERLY PATIENTS

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REMOVAL OF CYTOMEGALOVIRUS (CMV) INFECTED LEUCOCYTES FROM CMV SEROPOSITIVE BLOOD UNITS BY BEDSIDE BLOOD FILTRATION

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